Healthcare utilization among individuals diagnosed with lynch syndrome through a universal germline genetic testing program.
Authors: Heather Hampel, Ilana Solomon, Michael Garcia, Marilan Luong, Sarah Labib, Joseph D. Bonner, Lawrence Shaktah, Lauren Gima, Christine Hong, Gregory Idos, Sidney S. Lindsey, Kevin McDonnell, Wai Park, Katherine G. Roth, Elise Sobotka, Yi Xiao, Stanley R. Hamilton, Stephen B. Gruber, Stacy W. Gray
Journal: Journal of Clinical Oncology (2023)

10603 Background: Most individuals with Lynch syndrome (LS) are unaware of their risk. Criteria-based testing will not close this gap as it fails to identify ~50% of mutation carriers. Universal germline testing (GT) for in oncology stands to identify more mutation carriers and advance cancer control. However, the clinical utility of universal germline testing is unknown. Methods: The enterprise-wide City of Hope INSPIRE study offers all consented patients GT for cancer susceptibility (155 genes) and actionable disorders (59 genes). We used an informatics approach to evaluate healthcare utilization for patients found to have MLH1, MSH2, MSH6, PMS2 or EPCAM mutations. We queried codified data elements in our electronic data warehouse before and after GT (post testing interval: 1-29 months). We binned care as possibly related/ not related to HBOC based on NCCN guidelines. Results: Of 10,814 patients who had GT, 80 (0.74%) had a pathogenic/ likely pathogenic mutation in either MLH1, MSH2, MSH6, PMS2 or a 3’ deletion of EPCAM. The demographic distribution of LS patients was: white (n = 51, 64%), Asian (n = 13, 16%), Hispanic (n = 19; 24%); female (n = 51, 64%); the mean age was 54 yrs. Eighty-six percent (n = 69) had cancer, including 45% with cancers associated with LS (colorectal 17%, endometrial 7%, ovarian 6%, esophageal/stomach 5%, bladder/urinary tract 5%, and prostate 5%) and 41% with cancers that are not associated with LS. Fifty-two percent of all LS patients had procedures, imaging, and/or therapy potentially related to their LS diagnosis. As expected, utilization of colonoscopy, EGD, MRCP/EUS, transvaginal ultrasound, and hysterectomy with bilateral salpingo-oophorectomy (HBSO) occurred both before and after testing for the cancer cohort, with the majority of utilization occurring after testing likely related to their Lynch syndrome diagnosis. Twelve (17%) cancer patients with Lynch syndrome received Immune Checkpoint Inhibitor therapies. In the unaffected cohort, rates of utilization were higher prior to testing for transvaginal ultrasound possibly because 2% underwent a HBSO after their diagnosis and no longer required endometrial surveillance. Rates of colonoscopy, EGD, and HBSO were all higher after GT. Conclusions: We found high levels of relevant healthcare utilization for Lynch syndrome gene mutation carriers in the context of universal GT. However, this initial informatics approach is limited because key information on prior GT and motivations for surgery (e.g., therapeutic vs prophylactic HBSO) are not adequately captured in codified data. Codified EHR queries will need to be augmented by text mining and/or manual chart review to fully capture care and assess the clinical utility of system-wide genetic care delivery interventions.